This study examines global trends in cardiovascular disease (CVD) associated with kidney dysfunction (KD) from 1990 to 2021 and projects future trends through 2050.

This study analyzed the 2021 Global Burden of Disease (GBD) database, focusing on age-standardized mortality rate (ASMR), age-standardized disability-adjusted life years rate (ASDR), absolute numbers, estimated annual percentage change, and average annual percent change. A Bayesian age-period-cohort model was employed to project global trends from 2022 to 2050. Variables included age, gender, national levels, and Socio-demographic Index (SDI) regions.

From 1990 to 2021, the CVD burden from KD increased, with deaths rising from 1,312,393 to 2,095,800 and DALYs from 27,382,767 to 41,589,861. However, the ASMR decreased from 40.58 per 100,000 in 1990 to 25.55 in 2021, while ASDR fell from 742.17 to 489.81 during the same period. The burden was higher in men, peaking at ages 70-74 and in women at ages 85-89. Regions with lower-middle and low SDI recorded the highest CVD burden, inversely related to SDI levels. Geographically, Central Asia and Eastern Europe recorded the highest rates, while high-income Asia Pacific and Southern Latin America had the lowest. Projections suggest a sustained decline in global CVD burden due to KD from 2022 to 2050, although disparities between sexes are expected to persist, with men bearing a heavier burden.

CVD attributable to KD remains a major global public health challenge, especially for men, the elderly, and low SDI regions. These spatial and temporal variations highlight the need for region-specific healthcare strategies.

The transient receptor potential melastatin 2 (TRPM2) channel is a nonselective calcium channel that is sensitive to oxidative stress (OS), and is widely expressed in multiple organs, such as the heart, kidney, and brain, which is inextricably related to calcium dyshomeostasis and downstream pathological events. Due to the increasing global burden of kidney or cardiovascular diseases (CVDs), safe and efficient drugs specific to novel targets are imperatively needed. Notably, investigation of the possibility to regard the TRPM2 channel as a new therapeutic target in ROS-related CVDs or renal diseases is urgently required because the roles of the TRPM2 channel in heart or kidney diseases have not received enough attention and thus have not been fully elaborated. Therefore, we aimed to review the involvement of the TRPM2 channel in cardiovascular disorders related to kidney or typical renal diseases and attempted to speculate about TRPM2-mediated mechanisms of cardiorenal syndrome (CRS) to provide representative perspectives for future research about novel and effective therapeutic strategies.

These 4 hypothetical cases highlight new features of the American Heart Association cardiovascular-kidney-metabolic (CKM) health construct. The cases incorporate the CKM staging system, estimates from the PREVENT risk calculator, and clinical approaches related to CKM stages and individual risk profiles. Topics include management considerations for (1) a patient with stage 1 obesity and impaired glucose tolerance, (2) a patient with metabolic risk factors and moderate-risk chronic kidney disease (CKD), (3) a patient with subclinical atherosclerotic cardiovascular disease and multiple comorbid conditions, and (4) a patient with metabolic risk factors, prior myocardial infarction, new-onset heart failure, atrial fibrillation, and CKD.

Background/Objectives: In recent decades, shifting demographics and advancements in treating cardiovascular disease have altered the types of patients receiving coronary angiography (CA). However, data investigating the impact of kidney dysfunction stratified by the indication for CA are limited. Methods: Consecutive patients who underwent invasive CA at one institution between 2016 and 2022 were included in this study. Firstly, the prevalence and extent of coronary artery disease (CAD) in patients with different levels of kidney function was assessed. Secondly, the study examined how impaired kidney function affected long-term outcomes-specifically the risk of rehospitalization for heart failure (HF), acute myocardial infarction (AMI), or the need for coronary revascularization-at 36 months of follow-up. Results: A total of 7624 patients undergoing CA were included with a median estimated glomerular filtration rate (eGFR) of 68.9 mL/min/1.73 m2 (IQR: 50.8-84.3). In total, 63.7% of patients had an eGFR ≥ 60 mL/min/1.73 m2, 29.0% an eGFR of 30-<60 mL/min/1.73 m2, and 7.3% an eGFR of <30 mL/min/1.73 m2. Compared to patients with an eGFR ≥ 60 mL/min/1.73 m2, those with an eGFR 30-<60 mL/min/1.73 m2 and eGFR < 30 mL/min/1.73 m2 had a higher prevalence of CAD (66.8% vs. 72.9% and 80.1%, respectively; p = 0.001) and three-vessel CAD (25.6% vs. 34.5% and 39.5%, respectively; p = 0.001). At 36 months of follow-up, patients with an eGFR 30-<60 mL/min/1.73 m2 and eGFR < 30 mL/min/1.73 m2 suffered from significantly higher risk of HF-associated rehospitalization (HR = 1.937, 95% CI: 1.739-2.157, p = 0.001 and HR = 3.223, 95% CI: 2.743-3.787, p = 0.001, respectively) and AMI compared to patients with an eGFR ≥ 60 mL/min/1.73 m2 (reference group). The significantly higher risk of HF-related rehospitalization remained after multivariable adjustment. Conclusions: Both groups with impaired kidney function demonstrated a markedly higher risk of rehospitalization for HF at 36 months-even after multivariate adjustments. Increased risk of HF-related rehospitalization in patients with an eGFR < 30 mL/min/1.73 m2 was especially evident if they also presented with decompensated HF and LVEF < 35%. In patients with an eGFR 30-<60 mL/min/1.73 m2, presenting with angina pectoris and multivessel disease increased the risk of HF-related rehospitalization.

Ischemic stroke (IS) is a leading global cause of mortality and disability, particularly prominent in patients with end-stage renal disease (ESRD). Despite clinical evidence of their comorbidity, the molecular mechanisms underlying their interaction remain elusive. This study aims to identify shared biomarkers, gene regulatory networks, and therapeutic targets through integrative bioinformatics analyses. Gene expression datasets for IS (GSE16561, GSE22255) and ESRD (GSE37171, GSE142153) were obtained from gene expression omnibus (GEO). Weighted gene co-expression network analysis (WGCNA) and differential expression genes (DEGs) analysis identified shared genes and enriched pathways. Protein-protein interaction networks were constructed using STRING with clustering algorithms. Immune cell infiltration analysis was performed via CIBERSORT. Transcriptional regulatory networks were predicted using RcisTarget and miRcode. Key gene expressions were validated by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) in clinical samples. We identified 417 intersecting genes through WGCNA and 1712 shared differentially expressed genes. Among these, seven key genes (MRPL49, MRPS2, MRPS9, MRPS10, MRPS11, MRPS27, TFB1M) demonstrated central roles in mitochondrial function. Immune infiltration analysis revealed significant correlations with T cells and neutrophils. Pathway enrichment implicated these genes in transforming growth factor beta (TGF-β) signaling, p53 pathway, and G2/M checkpoint. Clinical validation confirmed significant downregulation of MRPS9, MRPS10, MRPS11, MRPS27 and TFB1M in comorbid patients. This study systematically elucidates the mitochondrial-immune interaction mechanisms in IS-ESRD comorbidity, highlighting the pivotal role of mitochondrial ribosomal protein (MRP) family genes in regulating cellular energetics and inflammatory responses. These findings provide new foundations for targeted therapies.

Social determinants of health (SDOH) contribute to increased cardiovascular disease (CVD) mortality.

The authors investigated the mediating effects of behavioral and clinical risk factors in the association between SDOH and CVD mortality.

A total of 50,808 National Health and Nutrition Examination Survey participants aged ≥20 years were included in this analysis. Data on social, behavioral, and clinical risk factors were collected in each National Health and Nutrition Examination Survey, and CVD deaths were ascertained through linkage to the National Death Index with follow-up through 2019. Multiple mediation analysis was used to examine the contributions of behavioral and clinical risk factors to the SDOH-CVD mortality association.

The mean age of participants was 47.2 years, and 48.8% were male. A dose-response association between the number of SDOH and CVD mortality was identified. Individuals with a composite SDOH score ≥ median have a 2.13-fold increased risk of CVD mortality (95% CI: 1.91-2.37) compared to those with a score < median. After adjusting for behavioral and clinical risk factors, the HR was reduced to 1.67 (95% CI: 1.50-1.86). Current smoking (relative contribution 11.4%; 95% CI: 8.1%-14.8%), physical inactivity (7.7%; 95% CI: 4.9%-10.6%), chronic kidney disease (5.5%; 95% CI: 3.8%-7.1%), diabetes (2.0%; 95% CI: 1.1%-2.9%), and unhealthy sleep duration (1.8%; 95% CI: 0.3%-3.3%) significantly mediated the association between CVD mortality and unfavorable SDOH. In aggregate, behavioral and clinical risk factors mediated 30.8% (95% CI: 24.2%-37.5%) of the overall CVD mortality attributable to unfavorable SDOH.

Behavioral and clinical risk factors partially mediate the association between unfavorable SDOH and increased CVD mortality.

This study investigates the association between intra-individual differences in estimated glomerular filtration rate based on serum creatinine (eGFRscr) and cystatin C (ΔeGFRcysc-scr) and incident CVD.

This study used data from the China Health and Retirement Longitudinal Study (CHARLS) from 2015 to 2020. ΔeGFRcysc-scr were determined by subtracting eGFRscr from eGFRcysc. The outcome was the incidence of CVD, including heart diseases, and stroke, obtained through self-reports. Cox proportional hazard regression models were employed to examine the association between ΔeGFRcysc-scr and CVD risks. Restricted cubic spline with three knots at the 10th, 50th, and 90th centiles was conducted to flexibly model the association. During this period, 1187 incident CVD events were documented. After adjusting for covariates, the risk of CVD was reduced by 13.2 % (Hazard ratio [HR] = 0.868; 95 % confidence interval [95 % CI]: 0.818-0.921) for every 15 mL/min/1.73 m2 increase in baseline ΔeGFRcysc-scr. Specifically, individuals in negative-ΔeGFRcysc-scr group (<-15 mL/min/1.73 m2) had a 33.6 % increased risk of CVD events (HR = 1.336; 95 % CI: 1.151-1.551), and positive-ΔeGFRcysc-scr group (≥15 mL/min/1.73 m2) had a 34.5 % decrease risk of CVD events (HR = 0.655; 95 % CI: 0.541-0.794), compared with those in reference group (-15 to 15 mL/min/1.73 m2). These associations remained robust after adjusting for potential confounders or sensitivity analysis.

Our findings suggest that intra-individual differences in eGFR estimates based on creatinine versus cystatin C are associated with CVD risk in the Chinese population. This highlights the potential value of using both markers for more accurate CVD risk stratification in clinical practice.

Type 4 cardiorenal syndrome (CRS) involves cardiovascular alterations caused by chronic kidney disease (CKD). Fibroblast growth factor-23 (FGF23), carboxy-terminal propeptide of procollagen type I (PIP), and parathyroid hormone (PTH) have been proposed as biomarkers of pathological cardiac remodeling in CKD. In contrast, it has been suggested that MicroRNA 221 has a cardioprotective role. Available evidence shows that, 12 months after kidney transplantation (KT), type 4 CRS reverts in only half of the patients.

To assess long-term cardiac reverse remodeling after KT and its association with FGF23, PIP, and PTH levels.

Patients with end-stage renal disease were assessed before and 28 months after KT using FGF23, PIP, and PTH serum concentrations and transthoracic echocardiography.

Fifty-three patients were followed for 28 months after KT. All the patients showed cardiac abnormalities upon inclusion. A follow-up assessment showed a reduction in left ventricle (LV) mass (121 ± 48 vs. 65 ± 14 gr/m2) and left atrial volume (46 vs. 30 ml/m2). The LV ejection fraction (53 vs. 63%), LV global longitudinal strain (-15.9 vs.-19.4%), and LV diastolic function improved. miR-221 expression increased after KT (8.73 RIQ= 3.7-25 vs. 40.16 RIQ= 24-223, p=0.001) and was correlated with the Ee´ratio (r= -0.32, p= 0.02). Multivariate analysis showed that post-KT LV mass was determined by pre-KT LV mass, serum Cr level, post-KT PIP, and hypertension (R2 = 0.65, F=12.1, p=0.001).

Contrary to other evidence, this study demonstrated that type 4 CRS is reversible over the long term. This is a paramount finding because KT normalizes cardiac structure and function independently of the severity of basal cardiac abnormalities.

Chronic kidney disease (CKD) patients show high rates of cardiovascular disease (CVD) and mortality. In the general population, obesity, hypertension, and diabetes are known as the classical CVD risk factors. However, CKD patients have other predisposing CVD factors more associated with bone and mineral metabolism disorders (BMD). BMD originates from reduced 1,25-dihydroxy vitamin D and hypocalcemia, which lead to secondary hyperparathyroidism, with increased parathyroid hormone (PTH) levels and hyperphosphatemia as the progression of renal damage. Due to their pleiotropic effects, vitamin D and its analogs, such as cholecalciferol, calcitriol, or paricalcitol, have proven effective in controlling BMD and CVD. On the other hand, visceral adiposity has been shown to increase the risk for CVD in both the general and CKD populations via complex autocrine and paracrine hormonal mechanisms. This seems to be the case with fat surrounding the epicardium. Although it has not been widely evaluated, the fat surrounding the kidneys, or the perirenal adipose tissue (PAT), could also share similarities with the epicardial in terms of its potential contribution to the CVD risk observed in these patients. We conducted a preliminary study to assess differences in PAT on a sample of patients with CKD presenting diverse CVD history and who were receiving different vitamin D-receptor activators.

An observational study was performed at UNIRENAL Center (Venezuela), from January to November 2015. Analytical and clinical parameters were evaluated. The PAT thickness was measured in centimeters through a B-mode ultrasound. Thus, we included 83 CKD patients treated with vitamin D or analogs (mean age 58.3 ± 16y); 57.83% were females. Nearly half of the sample was classified as CKD-G3 (n = 40). Prior history of CVD was present in 55.4% (N = 46) of participants. Must of the patients (n = 46;55.42%) receiving oral cholecalciferol (1000 IU/day) as part of the treatment for lower levels of vitamin D or BMD related to CKD (mainly elevated PTH), followed by those under calcitriol at 0.5 mcg/day (n = 27;32.53%), and around 12% (n = 10;12.05%) on paricalcitol (1 mcg/day). The mean treatment vintage was 20 ± 6 months for cholecalciferol, 18 ± 4 months for calcitriol, and 16 ± 2 months for paricalcitol. Those with a history of CVD (n = 46) showed higher levels of urea (mean 62.0vs45.2 mg/dl, p < 0.05), uric acid (mean 5.5vs4.3 mg/dl; p < 0.03), and iPTH (mean 186.2vs65.2pcg/dl; p < 0.05) than patients free of CVD events (n = 37). These findings were also in parallel with decreased renal function in the group with previous CVD history, as evidenced by a significantly lower eGFR (mean 53.55vs89.00 ml/min/1.73 m2,p < 0.001). Similarly, the mean PAT thickness was elevated in the group with a history of CVD in relation to those with no previous CVD events (0.99vs0.80 cm; SD ± 0.30;p ~ 0.05). The comparative analysis for the patients with prior cardiovascular events between the three treatments revealed that those on paricalcitol had lesser PAT accumulation than those treated with cholecalciferol or calcitriol (p < 0.05). In conclusion, our study shows that PAT thickness in CKD may be influenced by vitamin D analog-based treatment. Further research is needed to better understand the mechanistic links between PAT, BMD, and CVD in this population.

Clinical characteristics and outcomes of patients with myocardial infarction (MI) with nonobstructive coronary arteries (MINOCA) are not fully understood, particularly in Japan.

We enrolled a total of 8881 patients with acute MI from the Miyagi Acute Myocardial Infarction Registry Study (2012-2020), with a median age of 69 years. Among them, 239 patients (2.7%) were diagnosed with MINOCA. Compared with those with MI with obstructive coronary artery disease (MI-CAD), patients with MINOCA were more often women, had a higher incidence of non-ST-segment-elevation MI and a lower prevalence of dyslipidemia. Compared with patients with MI-CAD, patients with MINOCA in all age groups (<59, 60-69, 70-79, >80 years of age) had a higher incidence of non-ST-segment-elevation MI. Additionally, those ≤59 years of age were more often women and had a lower prevalence of diabetes and dyslipidemia. In-hospital mortality increased with age in patients with MI-CAD (3.9% for <59 years of age, 5.6% for 60-69 years of age, 8.3% for 70-79 years of age, and 15.2% for >80 years of age; P<0.01), but not in patients with MINOCA (4.5%, 7.4%, 6.0%, and 9.6%, respectively; P=0.36). Compared with patients with MI-CAD, patients with MINOCA had lower in-hospital mortality for Killip class IV (40.7% versus 20.0%; adjusted odds ratio [OR], 0.31 [95% CI, 0.10-0.94]; P=0.04) and renal dysfunction (20.0% versus 7.1%; adjusted OR, 0.29 [95% CI, 0.09-0.96]; P=0.04).

Patients with MINOCA exhibit distinct clinical characteristics and outcomes compared with those with MI-CAD, particularly in terms of age, sex, prevalence of comorbidities, and in-hospital mortality. These findings underscore the importance of tailored clinical approaches for patients with MINOCA.

Early neurological deterioration (END) frequently complicates acute ischemic stroke (AIS), worsening prognosis, particularly in patients with type 2 diabetes mellitus (T2DM), where hyperglycemia accelerates atherosclerosis, increasing both stroke risk and subsequent END. This study aimed to identify predictors of END in minor stroke patients with T2DM and develop a nomogram integrating these factors with intracranial atherosclerosis (ICAS) scores, evaluating its performance against various machine learning (ML) models.

We retrospectively analyzed clinical data from 473 minor stroke patients with T2DM treated at our hospital between January 2021 and December 2023. Utilizing LASSO and multivariate logistic regression, we identified characteristic predictors. The cohort was randomly allocated into training (n = 331) and validation (n = 142) groups. Six ML algorithms-SVM, LR, RF, CART, KNN, and Naive Bayes-were assessed, and nomograms were used to visualize the predictive model's performance, evaluated via Area Under the Curve (AUC), calibration plot, and Decision Curve Analysis (DCA).

The ICAS score has been recognized as a pivotal determinant of END, alongside four other significant factors: NIHSS score, low-density lipoprotein cholesterol (LDL-C) levels, presence of branch atheromatous disease (BAD), and stenosis of the responsible vessel ≥50%. The model demonstrated robust predictive capabilities, achieving strong performance in training (AUC = 0.795) and validation (AUC = 0.799) sets. This advanced ML model, which integrates biochemical and imaging indicators, enables accurate risk assessment for END in minor stroke patients with T2DM.

By integrating the ICAS score with the NIHSS score, LDL-C levels, presence of BAD, and stenosis of responsible vessels ≥50%, we developed a clinical model for predicting END in patients with minor stroke and T2DM. This model provides critical decision support for clinicians, facilitating early identification of high-risk patients, personalized treatment, and improved outcomes.

Lead is an environmental and occupational heavy metal and contaminant that can lead to chronic kidney disease (CKD). This study analyzed the long-term trend burden from 1990-2021 using Global Burden of Disease Study 2021, projecting trends through 2050 with Bayesian age-period-cohort models. In 2021, the number of deaths and disability-adjusted life years (DALYs) of lead-associated CKD was 8635.60 and 189127.20. And age-standardized mortality and DALYs rates were 0.47 per 100,000 population and 9.39 per 100,000 population, respectively. Compared with 1900, all indicators have declined except for death number, all of which were below global level. The sex-specific burden increased with increasing age, and was higher in males. The downward trend in sex-specific burden from 2020-2050 was observed. While overall burden has decreased, persistent environmental lead pollution necessitates targeted prevention for males and middle-aged/elderly populations. CKD management and pollution control remain critical public health challenges in China.

Megalin is an endocytic receptor in the proximal tubules that reabsorbs filtered proteins in the kidneys. Recycling of megalin after endocytosis and its expression on the apical plasma membrane of the proximal tubule are critical for its function. The expression of megalin in the kidney undergoes dynamic changes under physiologic and pathophysiologic conditions. Receptors and various effector signaling components regulate megalin expression and, potentially, function. Genetic manipulation and rare mutations in megalin suggest that a lack of or deficiency in megalin expression/function promotes tubular proteinuria and albuminuria. However, the role of megalin in kidney diseases associated with obesity, diabetes, hypertension, and nephrotoxicity remains unclear. To address these questions, animal and human studies have indicated megalin as a protective, injurious, and potentially urinary marker of nephropathy. This article reviews the literature on the regulation of megalin expression and the role of megalin in the pathophysiology of the kidney under experimental and clinical conditions. Moreover, this review articulates the need for studies that can clarify whether megalin can serve as a therapeutic target, in one way or the other, to treat kidney disease.

Podocytes are specialized cells within the glomerular filtration barrier, which are crucial for maintaining glomerular structural integrity and convective ultrafiltration. Podocytes exhibit a unique arborized morphology with foot processes interfacing by slit diaphragms, ladder-like, multimolecular sieves, which provide size and charge selectivity for ultrafiltration and transmembrane signaling. Podocyte dysfunction, resulting from oxidative stress, dysregulated prosurvival signaling, or structural damage, can drive the development of proteinuria and glomerulosclerosis in hypertensive nephropathy. Functionally, podocyte injury leads to actin cytoskeleton rearrangements, foot process effacement, dysregulated slit diaphragm protein expression, and impaired ultrafiltration. Notably, the renin-angiotensin system plays a pivotal role in podocyte function, with beneficial AT2R (angiotensin receptor 2)-mediated nitric oxide (NO) signaling to counteract AT1R (angiotensin receptor 1)-driven calcium (Ca2+) influx and oxidative stress. Disruption of this balance contributes significantly to podocyte dysfunction and drives albuminuria, a marker of kidney damage and overall disease progression. Oxidative stress can also lead to sustained ion channel-mediated Ca2+ influx and precipitate cytoskeletal disorganization. The complex interplay between GPCR (G-protein coupled receptor) signaling, ion channel activation, and redox injury pathways underscores the need for additional research aimed at identifying targeted therapies to protect podocytes and preserve glomerular function. Earlier detection of albuminuria and podocyte injury through routine noninvasive diagnostics will also be critical in populations at the highest risk for the development of hypertensive kidney disease. In this review, we highlight the established mechanisms of oxidative stress-mediated podocyte damage in proteinuric kidney diseases, with an emphasis on a hypertensive renal injury. We will also consider emerging therapies that have the potential to selectively protect podocytes from redox-related injury.

Objective Kidney failure increases people's risk of cardiovascular disease, sometimes requiring cardiac surgery. The aim of this study was to estimate the risk of cardiac surgery for adults with treated kidney failure in comparison with the general population in Australia. Methods We performed a population-based retrospective cohort study by linking data between the Australia and New Zealand Dialysis and Transplant Registry and the Australian and New Zealand Society of Cardiac and Thoracic Surgeons Cardiac Surgery Database, for 2010-2019. Age-sex-standardised surgery risk relative to the general population was estimated for adults receiving long-term dialysis and kidney transplant recipients, and subpopulations defined by procedure type, comorbidity, clinical status and dialysis-related factors. Results Among 1541 adults receiving treatment for kidney failure at the time of cardiac surgery in 2010-2019, the prevalence of comorbidity and risk factors was usually highest in those receiving dialysis, followed by transplant recipients and the general population (n =113,126). For all major cardiac surgical procedure types, the incidence of surgery for adults receiving dialysis and transplant recipients exceeded that for the general population (e.g. isolated coronary artery bypass grafting relative rates 15.3 [95% CI 13.7-17.0] and 2.0 [1.6-2.6] respectively). Relative incidence was especially high for the dialysis cohorts with insulin-treated diabetes and those with body mass index <25kg/m2 . Conclusions Adults with treated kidney failure had a higher risk of cardiac surgery than the general population in Australia in 2010-2019, especially when associated with diabetes. Data linkage between clinical quality registries enabled estimation of the extent of cardiac surgical burden.

Background/Objectives: Chronic kidney disease (CKD) is associated with increased annual costs, with the highest costs attributable to renal replacement therapy (RRT). These costs will rise as prevalence increases. Therefore, forecasting the future prevalence and economic burden of CKD, particularly in underdiagnosed populations, may provide valuable insights to policymakers looking at strategies to implement interventions to delay CKD progression. Methods: As part of the Inside CKD study, this work used epidemiological data to generate a virtual population representative of Poland that progressed through a microsimulation in 1-year increments between 2022 and 2027. This microsimulation was used to assess the clinical and economic burdens of CKD in Poland. Results: Between 2022 and 2027, the percentage of individuals with CKD is projected to increase from 10.7% to 11.3%. Only 30.1% of individuals with CKD will be diagnosed in 2027. During this time, the total healthcare cost of individuals with diagnosed CKD pre-RRT is predicted to decrease slightly from $73 million to $62 million. However, the total healthcare cost of individuals with diagnosed CKD is projected to increase by 23.1% when including RRT. Conclusions: This study shows that the clinical and economic burdens of individuals with CKD will worsen in the upcoming years. The implementation of policies to enhance the early detection of CKD and the initiation of treatments to slow disease progression should be implemented to reduce the number of individuals requiring RRT.

Acute kidney injury (AKI) is a common clinical occurrence causing high mortality and morbidity. In acute renocardiac syndrome, AKI leads to acute cardiac injury or/and dysfunction. This study aimed to investigate the antioxidative effects of Edaravone on cardiac tissues following the induction of renal ischemia-reperfusion injury (IRI) in rats.

Twenty-four male Wistar rats were randomly divided into four groups: IR+Edaravone, Edaravone, IR, and Sham groups (six rats per group). Non-traumatic clamps were used to stop the artery and vein blood flow of the left kidney in rats of the IR groups for 45 minutes. Thirty minutes before ischemia induction, Edaravone (3 mg/kg) was injected intraperitoneally in the IR+Edaravone group. Cardiac samples were subjected to biochemical analyses.

The Results showed a significant increase in the enzymatic activity of glutathione peroxidase (P=0.01), catalase (P=0.03), and superoxide dismutase (P=0.02), and the levels of glutathione (P=0.012), and total antioxidant capacity (P<0.001) in the IR+Edaravone group in comparison to the IR group. Moreover, the total antioxidant capacity of the heart was increased in the Edaravone group compared to the control and IR groups (P<0.001), indicating the safety of the drug.

The results can reveal important insights into the protective effects of Edaravone against acute renocardiac syndrome.

Studies on the relationship between serum sex hormone-binding globulin (SHBG) levels and chronic kidney disease (CKD) remain limited and inconclusive. Therefore, this study aims to evaluate the effects of SHBG on CKD in a nationally representative population. We included a total of 7713 adults from the National Health and Nutrition Examination Survey (NHANES) conducted between 2013 and 2016. Multivariate logistic regression models were utilized to evaluate the association between SHBG levels and CKD, and odds ratios (ORs) and 95% confidence intervals (CIs) were calculated. Additionally, we employed a restricted cubic-spline regression model to explore potential dose-response associations. Among the participants, 4030 (52.2%) were women, and CKD was observed in 13.50% (1043/7713). After adjusting for various variables, SHBG levels were found to be associated with the risk of CKD (OR: 1.24; 95% CI: 1.11-1.38), indicating a 24% higher risk of CKD for SHBG levels (log2-transformed). A comparison between the highest quartile (Q4) and the lowest quartile (Q1) of SHBG levels revealed an OR of 1.51 (95% CI: 1.17-1.95) for CKD prevalence. Notably, while the association between SHBG and the risk of CKD disappeared when SHBG levels were <46.1 nmol/l, it existed when SHBG levels exceeded 46.1 nmol/l. Taken together, these findings indicate nonlinear correlations between serum SHBG levels and CKD, with the inflection point occurring at approximately 46.1 nmol/l, which suggest that SHBG levels could serve as a useful marker for assessing CKD risk, with potential applications in early detection and management strategies.

Literature on the association between the cardiometabolic index (CMI) and chronic kidney disease (CKD) risk is limited, especially in hypertensive populations. The objective of the present investigation was to assess the relationship between the CMI and CKD risk in a hypertensive population. The current cross-sectional study included a total of 13 717 individuals with hypertension. The calculation of the CMI was based on the waist-to-height ratio and the triglyceride-to-high-density lipoprotein cholesterol ratio. The definition of CKD was based on an estimated glomerular filtration rate (eGFR) of less than 60 mL/min/1.73 m2. The prevalence of CKD was found to be 4.24% in younger adults (aged < 65 years) and 14.93% in the elderly (aged ≥ 65 years). The results of the multivariate regression analysis indicated that in the elderly group, the CMI was positively associated with CKD risk (odd ratio [OR] 1.29; 95% confidence interval [CI]: 1.14, 1.46), while no significant relationship was observed in the younger group (OR 1.04, 95% CI: 0.85, 1.27). Furthermore, subgroup analyses did not identify any potential factors that could modify the relationship between the CMI and CKD risk (all p for interaction > 0.05). Among adults with hypertension, there was an independent and positive correlation between the CMI and CKD risk in the elderly, whereas such a correlation was not observed in younger adults. Trial Registration: ClinicalTrials.gov identifier: ChiCTR1800017274 [China Hypertension Registry Study].

Kidney dysfunction (KD) poses a severe threat to human health. The aim of this study is to gain a comprehensive understanding of the trends in cardiovascular disease (CVD) burden attributable to KD, thereby providing a theoretical basis for relevant public health policies.

This study analyzed trends in the burden of CVD attributable to KD using the 2021 Global Burden of Disease data. It also examined the differences in mortality rates across various age groups, genders, and subtypes of CVD. Additionally, the age-period-cohort model combined with joinpoint regression analysis was employed to gain further insights into the changing trends and inflection points of CVD-related mortality.

In 2021, the global number of deaths from CVD attributable to KD significantly increased compared to 1990. However, the global age-standardized mortality rate (ASMR) decreased in 2021. The burden of CVD due to KD was particularly heavy among the elderly. Analysis using the age-period-cohort model revealed a decline in CVD-related mortality rates, with similar trends observed for both men and women.

This study reveals that although the ASMR for CVD due to KD is on a declining trend globally, the absolute number of deaths has significantly increased. This trend is especially pronounced among individuals aged 80 and older, males, and regions with a middle socio-demographic index (SDI). In the context of global aging, the burden of CVD related to KD is becoming increasingly substantial.

Background. Cardiovascular (CV) diseases are the most common causes of morbidity and mortality in hemodialysis (HD) patients. We studied the effect of high visit-to-visit ultrafiltration (UF) variability on CV abnormalities in HD patients. Methods. Twenty-nine consecutive patients (age: 65.6 ± 10.4 years) were recruited. Samples for routine lab tests were drawn pre-HD for syndecan-1 (SDC-1) and endothelin-1 (ET-1) measurements pre-, mid- and post-HD. Applanation tonometry was performed pre-, mid- and post-HD. Visit-to-visit ultrafiltration volume variability (UVSD) was calculated as the standard deviation of the UF volume/dialysis session in the preceding 12 months. Echocardiography was performed post-HD. Results. Patients were divided into two groups based on the median of UVSD (500 mL). The average UF volume/HD was not different between the groups. Blood pressure (BP) values were similar. Pre-HD cfPWV (10.75 m/s) was lower in the high UVSD group (14.1 m/s, p = 0.03). In the high UVSD group, post-HD cfPWV (13.9 m/s) was higher than the pre-HD cfPWV (p < 0.05). Pre-HD ET-1 was lower in the high UVSD group (8.6 ± 3.9 vs. 10.8 ± 2.7 pg/mL, p < 0.05). Left ventricular end-diastolic diameter (LVEDD) and left ventricular mass index (LVMI) were higher in the high UVSD group (55.7 ± 7.3 vs. 51.0 ± 5.4 mm and 449.9 ± 180.5 vs. 350.3 ± 85.9 g/m², p < 0.005, respectively). Left ventricular ejection fraction (LVEF) was lower in the high UVSD group (53.5 vs. 60, p < 0.05). Conclusions. High UVSD was associated with increased left ventricular hypertrophy and dysfunction and decreased LVEF compared to low visit-to-visit UV variability despite similar UF volumes temporarily compensated by more elastic arteries. The observed abnormalities may increase CV risk.

Incident chronic kidney disease (CKD) varies in populations with hypertension of similar severity. Proteinuria promotes CKD progression in part due to activation of plasminogen to plasmin in the podocytes, resulting in oxidative stress-mediated injury. Additional mechanisms include deficiency of renal alpha-klotho, that inhibits Wnt/beta-catenin, an up regulator of intra-renal renin angiotensin system (RAS) genes. Alpha-klotho deficiency therefore results in upregulation of the intra-renal RAS via Wnt/beta-catenin. In hypertensive, Dahl salt sensitive (DS) and spontaneously hypertensive rats (SHR), we investigated renal and vascular injury, miR-155, AT1R, alpha-klotho, and TNF-α. Hypertensive high salt DS (DS-HS), but not SHR developed proteinuria, plasminuria, and glomerulosclerosis. Compared to DS low salt (DS-LS), in hypertensive DS-HS alpha-klotho decreased 5-fold in serum and 2.6-fold in kidney, whereas serum mir-155 decreased 3.3-fold and AT1R increased 52% in kidney and 77% in aorta. AT1R, alpha-klotho, and miR-155 remained unchanged in prehypertensive and hypertensive SHR. TNF-α increased by 3-fold in serum and urine of DS-HS rats. These studies unveiled in salt sensitive DS-HS, but not in SHR, a genetically conditioned dysfunction of the intermolecular network integrated by alpha-klotho, RAS, miR-155, and TNF-α that is at the helm of their end-organ susceptibility while plasminuria may participate as a second hit.

The urine albumin (Alb)-to-creatinine (Crn) ratio (UACR) is a sensitive and early indicator of chronic kidney disease (CKD) and cardiorenal syndrome. This study developed a portable and wireless electrochemical-sensing platform for the sensitive and accurate determination of UACR. The developed platform consists of a carbon nanotube (CNT)-2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid)(ABTS)-based modified UACR sensor, a miniaturised potentiostat, a cup holder embedded with a magnetic stirrer and a smartphone app. The UACR sensing electrode is composed of two screen-printed carbon working electrodes, one screen-printed carbon counter electrode and a screen-printed AgCl reference electrode. The miniaturised potentiostat, which is controlled by the developed app, performs cyclic voltammetry and amperometry to detect Alb and Crn, respectively. Clinical trials of the proposed system by using spot urine samples from 30 diabetic patients indicate that it can accurately classify all three CKD risk statuses within 30 min. The high accuracy of our proposed sensing system exhibits satisfactory agreement with the commercial biochemical analyser TBA-25FR (Y = 0.999X, R2 = 0.995). The proposed UACR sensing system offers a convenient, reliable and affordable solution for personal mobile health monitoring and point-of-care urinalysis.

Background/Objectives: Numerous risk factors associated with development of cardiovascular disease (CVD) have been unfavorably altered in patients with chronic kidney disease (CKD). Low omega-3 polyunsaturated fatty acid (PUFA) intake and vitamin D deficiency are potential cardiometabolic risk factors in patients with CKD. The aim of this study was to evaluate dietary intake and status of omega-3 PUFA and vitamin D in pre-dialysis and hemodialysis patients and to examine the association of dietary α-linolenic acid (ALA) and fish consumption with blood pressure and carotid intima-media thickness (C-IMT), representing a non-invasive marker of atherosclerosis in CKD patients. Methods: All 77 selected patients (36 pre-dialysis, 41 on hemodialysis) underwent standardized clinical, nutritional, and laboratory assessments. Repeated 24 h recalls were performed to assess dietary intake. The fatty acid profile was determined by gas-liquid chromatography. Results: Inadequate vitamin D intake and vitamin D status were found in 95% of patients. PUFA profiles did not differ between hemodialysis and pre-dialysis participants. Dietary intake of ALA was negatively correlated with systolic blood pressure (SBP) (p = 0.013), C-IMT (p = 0.002), serum CRP (p = 0.044), iPTH (p = 0.01), and 25(OH)D3 (p = 0.006). ALA intake of more than 0.23 g daily was linked with lower SBP (p = 0.001), serum 25(OH)D3 (p = 0.004), and C-IMT (p = 0.002). Conclusions: This study contributes to a better understanding of the relationship between dietary ALA intake and C-IMT in CKD. The results of this study could emphasize the significant role of the high prevalence of vitamin D deficiency and inadequate omega-3 PUFA intake and status regarding CVD health in CKD patients.

The global status of chronic kidney disease (CKD) is underestimated, particularly the burden on adolescents and young adults (early-onset, aged 15-39).

We aim to investigate the pattern and trend of early-onset CKD from 1990 to 2019.

We analyzed age-specific rates of early-onset CKD incidence, death, and disability-adjusted life years (DALY) using Global Burden of Disease Study 2019 data. We examined the global, regional, national, gender-based, age group-based, and temporal changes of early-onset CKD burden from 1990 to 2019, as well as proportional DALY attributions of various risk factors.

From 1990 to 2019, the global age-specific incidence rate (per 100,000 population) significantly increased from 25.04 (95% confidence interval 18.51, 31.65) to 32.21 (23.73, 40.81) for early-onset CKD. However, the global age-specific death rate significantly decreased from 2.96 (2.76, 3.15) to 2.86 (2.61, 3.11), and the age-specific DALY rate remained stable. Regarding sociodemographic indexes (SDI), countries with middle SDI had the highest incidence rates and the fastest increasing trends, while those with low and low-middle SDI experienced the highest death and DALY rates. Women had a generally higher age-specific incidence rate than men, whereas men showed higher age-specific death and DALY rates. In addition, the burdens of CKD increased with age among adolescents and young adults. Moreover, the main attributable risk factors for DALY of early-onset CKD were high systolic blood pressure (SBP), fasting plasma glucose (FPG), and body mass index (BMI).

The age-specific incidence rate of early-onset CKD increased significantly from 1990 to 2019, and the age-specific DALY rate remained stable. High SBP, high FPG, and high BMI were the primary risk factors. Targeted prevention and healthcare measures should be developed considering age, gender, and region.

The PROGRESER study is a multicentre, prospective, observational, 3-year follow-up study of a cohort of patients with stage 3 chronic kidney disease (CKD) from different nephrology departments of hospitals in the Spanish healthcare system. The primary study objective was to analyse risk factors for CKD progression, identifying possible differences between patients with and without diabetes mellitus (DM). The secondary objective was to analyse if the cardiovascular risk factors were also associated with CKD progression.

A total of 462 patients (342 men and 120 women; mean age 66.5 ± 11.5 years) were recruited from 25 participating sites in Spain. Clinical, epidemilogical and analytical data were recorder in an electronic registrer each six months. Biological samples were obtained and frozen for a biobank record at baseline and at 18 and 36 months.

The initial mean glomerular filtration rate estimated by MDRD and after that reestimated by CKD-EPI was 43.9 ± 7.9 mL/min/1.73 m2; and 29 ± 6,8 mL/min/1,73 m2 at 3 years. 27.3% of patients had microalbuminuria and 22.5% had macroalbuminuria. Two-thirds of the patients (66.2%) presented renal damage progression according to the study criteria (decrease of more than 15% in eGFR over the baseline value). 38.7% presented a reduction in eGFR ≥ 30%; 20.3% had a reduction in eGFR ≥40%; 10.4% had a reduction ≥50% and 6.9% had a reduction ≥57%. Of the 199 diabetics, 134 (67.3%) suffered renal damage progression. Of the 263 non-diabetics, 172 (65.3%) presented progression (p = 0.456). 27.3% of patients had microalbuminuria and 22.5% proteinuria. The study found that CKD progression to a higher stage was not greater in diabetic compared to non-diabetic patients. Multivariate analysis revealed that the presence of arterial hypertension bordered on significance as a progression factor in non-diabetic patients (p = 0.07), and that, in diabetic patients, lower calcium levels and elevated intact parathyroid hormone levels at baseline were associated with progression.

in our study we have not found new factors for progression of renal damage, different from the yet well known traditional factors. DM "per se" was not a differential factor for progression in relation with non DM patients. Progression of renal damage in patients with CKD-3 KDOQI may be interpreted in a multifactorial context. The search for new biomarkers, different from traditional ones, is necessary to establish new therapeutic strategies to prevent the progression of CKD.

Diabetes, a chronic disease characterized by hyperglycemia, is associated with significantly accelerated complications, including diabetic kidney disease (DKD), which increases morbidity and mortality. Hyperglycemia and other diabetes-related environmental factors such as overnutrition, sedentary lifestyles, and hyperlipidemia can induce epigenetic changes. Working alone or with genetic factors, these epigenetic changes that occur without alterations in the underlying DNA sequence, can alter the expression of pathophysiological genes and impair functions of associated target cells/organs, leading to diabetic complications like DKD. Notably, some hyperglycemia-induced epigenetic changes persist in target cells/tissues even after glucose normalization, leading to sustained complications despite glycemic control, so-called metabolic memory. Emerging evidence from in vitro and in vivo animal models and clinical trials with subjects with diabetes identified clear associations between metabolic memory and epigenetic changes including DNA methylation, histone modifications, chromatin structure, and noncoding RNAs at key loci. Targeting such persistent epigenetic changes and/or molecules regulated by them can serve as valuable opportunities to attenuate, or erase metabolic memory, which is crucial to prevent complication progression. Here, we review these cell/tissue-specific epigenetic changes identified to-date as related to diabetic complications, especially DKD, and the current status on targeting epigenetics to tackle metabolic memory. We also discuss limitations in current studies, including the need for more (epi)genome-wide studies, integrative analysis using multiple epigenetic marks and Omics datasets, and mechanistic evaluation of metabolic memory. Considering the tremendous technological advances in epigenomics, genetics, sequencing, and availability of genomic datasets from clinical cohorts, this field is likely to see considerable progress in the upcoming years.

Cardiovascular disease (CVD) represents the primary cause of mortality in patients afflicted with end-stage renal disease and undergoing peritoneal dialysis (PD) treatment. Galectin-3 (Gal-3), a molecule known to exhibit a correlation with CVD mortality garners considerable interest. The objective of this study was to explore the potential association between serum Gal-3 levels and other CVD risk factors among PD patients.

In this cross-sectional study, a total of 114 PD patients with a minimum of 3 months of PD treatment were enrolled. Serum Gal-3 levels were quantified using an enzyme-linked immunosorbent assay. The data of patients with Gal-3 levels higher and lower than 26.744 pg/ml were compared using Mann-Whitney U tests or t tests. Pearson's correlation or Spearman's correlation analysis and multivariate regression were used to assess the associations between the known risk factors for CVD and Gal-3.

In comparison to the inter-group baseline data, the low Gal-3 group exhibited a higher glomerular filtration rate (GFR). Gal-3 levels correlate positively with PD duration, B-type natriuretic peptide (BNP), growth differentiation factor 15 (GDF-15), interventricular septal thickness in diastolic (IVST), and left ventricular mass index (LVMI). Conversely, Gal-3 exhibited a negative correlation with albumin levels. Multivariate linear regression analysis demonstrated a positive correlation between Gal-3 levels and BNP, GDF-15, PD duration, IVST and LVMI. Gal-3 levels were negatively correlated with albumin levels.

Gal-3 was strongly associated with BNP, GDF-15, IVST and LVMI in patients undergoing PD treatment. Prospective studies should be carried out to determine whether Gal-3 can be a promising biomarker in predicting increased risk of adverse cardiovascular events in PD patients.

Diabetes mellitus has emerged as a pressing global concern, with a notable increase in recent years. Despite advancements in treatment, existing medications struggle to halt the progression of diabetes and its associated complications. Increasing evidence underscores inflammation as a significant driver in the onset of diabetes mellitus. Therefore, perspectives on new therapies must consider shifting focus from metabolic stress to inflammation. High mobility group box (HMGB-1), a nuclear protein regulating gene expression, gained attention as an endogenous danger signal capable of sparking inflammatory responses upon release into the extracellular environment in the late 1990s.

Given the parallels between inflammatory responses and type 2 diabetes (T2D) development, this review paper explores HMGB-1's potential involvement in onset and progression of diabetes complications. Specifically, we will review and update the understanding of HMGB-1 and its inflammatory pathways in insulin resistance, diabetic nephropathy, diabetic neuropathy, and diabetic retinopathy.

HMGB-1 and its receptors i.e. receptor for advanced glycation end-products (RAGE) and toll-like receptors (TLRs) present promising targets for antidiabetic interventions. Ongoing and future projects in this realm hold promise for innovative approaches targeting HMGB-1-mediated inflammation to ameliorate diabetes and its complications.

A growing population of patients with chronic kidney disease (CKD) presents with non-ST-segment-elevation myocardial infarction, although little is known about their longer-term mortality.

Using the MINAP (Myocardial Ischaemia National Audit Project) registry, linked to Office for National Statistics mortality data, we analyzed 363 559 UK patients with non-ST-segment-elevation myocardial infarction, with or without CKD. Cox regression models were fitted, adjusting for baseline demographics. Compared with patients without CKD, patients with CKD were less frequently prescribed P2Y12 inhibitors (89% versus 86%, P<0.001) less likely to undergo invasive angiography (67% versus 41%, P<0.001) or percutaneous coronary intervention (41% versus 25%, P<0.001), and were less often referred to cardiac rehabilitation (80% versus 66%, P<0.001). Following non-ST-segment-elevation myocardial infarction, patients with CKD had higher risk of 30-day (adjusted hazard ratio [HR], 1.24 [95% CI, 1.20-1.29], 1-year 1.47 [95% CI, 1.44-1.51]) and 5-year mortality 1.55 (95% CI, 1.53-1.58) than patients without CKD (all P<0.001). Risk of mortality over the entire study period was highest in CKD Stage 5 (HR, 2.98 [95% CI, 2.87-3.10]), even after excluding mortality ≤30 days (HR, 3.03 [95% CI, 2.90-3.17]) (P<0.001). There was no significant difference in proportion of deaths attributable to cardiovascular disease at 30 days (CKD; 76% versus no CKD; 76%), or 1 -year (CKD; 62% versus no CKD; 62%).

Patients with CKD were significantly less likely to receive invasive investigation or undergo percutaneous coronary intervention and had significantly higher risk of short- and longer-term mortality. Risk of mortality increased with reducing CKD stage. Cardiovascular disease was the main cause of mortality in patients with CKD, but at comparable rates to the general population with non-ST-segment-elevation myocardial infarction.

Early detection of chronic kidney disease (CKD) is important because it enables clinicians to initiate effective treatment, preventing loss of kidney function, and delaying or avoiding progression to kidney failure. This study was aimed to assess knowledge, attitude, and practices towards prevention and early detection of CKD and associated factors.

Institution based cross-sectional survey was done at Adama Hospital Medical College, Ethiopia, between November 24/2021 and December 24/2021 among 190 hypertensive patients. Data were entered into EpiData version 4.2.0.0 and analyzed by Statistical Package for Social Sciences (SPSS) version 23.

The level of good knowledge, positive attitude, and good practice was 40.5%, 53.7%, and 47.4%, respectively. Government employed (AOR = 3.30, 95%CI: 1.38, 7.90), having an average monthly income of ≥3000 ETB (61.43 US dollars) (AOR = 2.95, 95%CI: 1.31, 6.66), and having a duration of ≥4 years since diagnosis of hypertension (AOR = 2.37, 95%CI: 1.11, 5.06) were factors significantly associated with good knowledge. Government employed (AOR = 2.56, 95%CI: 1.12, 5.87), having duration of hypertension ≥4 years since diagnosis (AOR = 2.16, 95%CI: 1.07, 4.36) were factors significantly associated with positive attitude. Government employed (AOR = 4.16, 95%CI: 1.38, 12.58), having an average monthly income of ≥3000 ETB (61.43 US dollars) (AOR = 6.74, 95%CI: 2.93, 15.52), having good knowledge towards prevention and early detection of CKD (AOR = 2.57, 95%CI: 1.14, 5.80) were significantly associated with good practice.

The level of good knowledge, positive attitude, and good practice towards was low. Educational programs on these issues are required to minimize the burdens.

Oxidative stress (OxSt) and inflammation are common in CKD and are known CV and mortality risk factors. In peritoneal dialysis (PD) OxSt and Inflammation even increase due to the use of glucose-based solutions.

This study analyzed in 15 PD patients the effect of 3 and 6 months of treatment with icodextrin-based glucose-free solutions on OxSt and inflammation, evaluating p22phox protein expression (Western blot), NADPH oxidase subunit, essential for OxSt activation, MYPT-1 phosphorylation state, marker of RhoA/Rho kinase pathway (ROCK) activity, involved in the induction of OxSt (Western blot) and Malondialdehyde (MDA) production (fluorimetric assay). Interleukin (IL)-6 blood level (chemiluminescence assay) has been measured and used as a marker of inflammation.

p22phox protein expression, MYPT 1 phosphorylation, and MDA were reduced after 3 months from the start of icodextrin (1.28 ± 0.18 d.u. vs. 1.50 ± 0.19, p = 0.049; 0.89 ± 0.03 vs. 0.98 ± 0.03, p = 0.004; 4.20 ± 0.18 nmol/mL vs. 4.84 ± 0.32 nmol/mL, p = 0.045, respectively). In a subgroup of 9 patients who continued the treatment up to 6 months, MYPT-1 phosphorylation was further reduced at 6 months compared to baseline (0.84 ± 0.06 vs. 0.99 ± 0.04, p = 0.043), while p22phox protein expression was reduced only at 6 months versus baseline (1.03 ± 0.05 vs. 1.68 ± 0.22, p = 0.021). In this subgroup, MDA was reduced at 6 months versus baseline (4.03 ± 0.24 nmol/mL vs. 4.68 ± 0,32, p = 0.024) and also versus 3 months (4.03 ± 0.24 vs. 4.35 ± 0.21, p = 0.008). IL-6 level although reduced both at 3 and 6 months, did not reach statistical significance.

The reduction of OxSt with icodextrin-based PD solutions, although obtained in a small patients cohort and in a limited time duration study, strongly supports the rationale of using osmo-metabolic agents-based fluids replacing glucose-based fluids. Ongoing studies with these agents will provide information regarding preservation of peritoneal membrane integrity, residual renal function, and reduction of CVD risk factors such as OxSt and inflammation.

Observational studies have identified that declined kidney function was associated with a higher risk of cardiovascular disease (CVD). However, the causation of such associations requires further exploration. Here, we compared the observational associations of various kidney function measurements with CVD and its major subtypes and further assessed the potential causality using Mendelian randomization (MR) analyses with individual-level data of 306,246 participants from the UK Biobank and genome-wide association study summary-level data from FinnGen consortium, Coronary ARtery DIsease Genome wide Replication and Meta-analysis plus The Coronary Artery Disease Genetics (CARDIoGRAMplusC4D) consortium, and MEGASTROKE Consortium, respectively. Kidney function measurements included circulating levels of cystatin C and creatinine, urine albumin-to-creatinine ratio (uACR), and estimated glomerular filtration rates (eGFR) from three chronic kidney disease epidemiology collaboration formulae (i.e., that using cystatin C, creatinine, and both). In the observational analyses, decreased kidney function measurements were associated with a higher risk of CVD in the UK Biobank study. For example, per one standard deviation decrease in baseline estimated glomerular filtration rates using both cystatin C and creatinine (eGFRcys + cre) was associated with 11% higher risk of CVD (hazard ratio = 0.89; 95% confidence interval, 0.87-0.90). In contrast, two-sample MR analyses did not suggest significant associations of any genetically instrumented kidney function measurement with the risk of CVD or its subtypes. Our findings suggested the inverse associations of kidney function measurements with CVD risk from observational studies were not supported by large MR analyses.

The online version contains supplementary material available at 10.1007/s43657-023-00145-7.

Left ventricular hypertrophy (LVH) in patients with end stage renal disease undergoing renal replacement is linked to an increased risk for cardiovascular diseases. Dialysis does not completely prevent or correct this abnormality, and the evidence for kidney transplantation (KT) varies. This analysis aims to explore the relationship between KT and LVH.

MEDLINE and Scopus were systematically searched in October 2023. All cross-sectional and longitudinal studies that fulfilled our inclusion criteria were included. Outcome was left ventricular mass index (LVMI) changes. We conducted a meta-analysis using a random effects model. Meta-regression was applied to examine the LVMI changes dependent on various covariates. Sensitivity analysis was used to handle outlying or influential studies and address publication bias.

From 7416 records, 46 studies met the inclusion criteria with 4122 included participants in total. Longitudinal studies demonstrated an improvement of LVMI after KT -0.44 g/m2 (-0.60 to -0.28). Blood pressure was identified as a predictor of LVMI change. A younger age at the time of KT and well-controlled anemia were also associated with regression of LVH. In studies longitudinally comparing patients on dialysis and renal transplant recipients, no difference was detected -0.09 g/m2 (-0.33 to 0.16). Meta-regression using changes of systolic blood pressure as a covariate showed an association between higher blood pressure and an increase in LVMI, regardless of the modality of renal replacement treatment.

In conclusion, our results indicated a potential cardiovascular benefit, defined as the regression of LVH, after KT. This benefit was primarily attributed to improved blood pressure control rather than the transplantation itself.

Cardiovascular disease is the cause of death in ≈50% of hemodialysis patients. Accumulation of uremic solutes in systemic circulation is thought to be a key driver of the endothelial dysfunction that underlies elevated cardiovascular events. A challenge in understanding the mechanisms relating chronic kidney disease to cardiovascular disease is the lack of in vitro models that allow screening of the effects of the uremic environment on the endothelium. Here, a method is described for microfabrication of human blood vessels from donor cells and perfused with donor serum. The resulting donor-derived microvessels are used to quantify vascular permeability, a hallmark of endothelial dysfunction, in response to serum spiked with pathophysiological levels of indoxyl sulfate, and in response to serum from patients with chronic kidney disease and from uremic pigs. The uremic environment has pronounced effects on microvascular integrity as demonstrated by irregular cell-cell junctions and increased permeability in comparison to cell culture media and healthy serum. Moreover, the engineered microvessels demonstrate an increase in sensitivity compared to traditional 2D assays. Thus, the devices and the methods presented here have the potential to be utilized to risk stratify and to direct personalized treatments for patients with chronic kidney disease.